Topical Tritiated Thymidine for Epidermal Growth Fraction Determination

Direct autoradiographic identification of the epidermal growth fraction (GF) requires the delivery of tritiated thymidine ([3H]dThd) to the skin during the time interval of an entire cell cycle. The GF in normal human epidermis has not been directly measured using this technique because the systemic infusion of radioactive [3H]dThd in benign skin conditions is precluded by ethical considerations. Studies were undertaken to assess the feasibility of measuring the epidermal GF in vivo by the topical delivery of [3H]dThd. The percutaneous penetration of [3dThd in various vehicles was evaluated to select an effective topical delivery system. A vehicle consisting of Azone, isopropanol, and water (2:49:49) was the best of 4 different vehicles tested. The optimal penetration of [3H]dThd, with respect to the concentration of Azone over a range of 0–4%, was achieved at 2%. During the initial 24h following a single topical application of [3H]dThd to hairless mice the labeling increased linearly with time. In vivo studies in hairless mice produced a GF of 95% by both continuous systemic [3H]dThd infusion, and by twice daily topical [3H]dThd. Azone vehicles induced epidermal hyperplasia which was minimized by lowering the Azone concentration and by decreasing the frequency of applications from 24 to 48h. These studies establish the rationale for using topical delivery of [3H]dThd for the in vivo measurement of epidermal GF

A practical guide to assessment of ventricular diastolic function using doppler echocardiography

AbstractDoppler assessment of diastolic function has become a standard part of routine echocardiographic examination and imparts information relevant to a patient's functional class, management and prognosis. This review describes the Doppler patterns of diastolic function relative to physical signs and physiology. A continuum of Doppler patterns of diastolic function exists, including normal diastolic function, impaired relaxation, pseudonormal filling, restriction, constriction and tamponade. These patterns evolve from one to another in a single individual, with changes in disease evolution, treatment and loading conditions. New applications of continuous wave Doppler, color Doppler M-mode and Doppler tissue imaging are refining our understanding of diastolic function

Valuing Rigor in the Risk Management Process

NASA, as an organization, takes risk management (RM) seriously, and for most projects, the risk management process is exemplar. There can be challenges, though, with defining RM processes. For example, many different risk analysis methodologies are available, they can be applied with varying degrees of rigor, and they can have different value depending on how projects use them. In particular, risk analysis methodologies vary considerably in the level of quantitative detail, with more probabilistic techniques encouraged in some situations. We discussed these processes and methodologies with ten project managers (PM) at the NASA Goddard Space Flight Center (GSFC). Our intent was not to prove with some level of statistical significance that some are more helpful than others, but rather to obtain a general understanding of how projects are identifying, and thinking, about risks. This paper describes some of the available risk processes and methodologies, and provides some insights about the benefits that can gained from their use. We provide an in-depth discussion of one quantitative methodology, Probabilistic Risk Assessments (PRAs), and conclude with a few insights from observed best practices

Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study.

Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist

Differentiation of constrictive pericarditis from restrictive cardiomyopathy by Doppler transesophageal echocardiographic measurements of respiratory variations in pulmonary venous flow

AbstractObjectives. The purpose of this study was to test the utility of measuring respiratory variation in pulmonary venous flow by transesophageal echocardiography.Background. Respiratory variation of atrioventricular and central venous flow velocities by Doppler echocardiography has been used to differentiate constrictive pericarditis from restrictive cardiomyopathy.Methods. We performed pulsed wave Doppler transesophageal echocardiography of the left or right pulmonary veins in 31 patients with diastolic dysfunction. Fourteen patients had constrictive pericarditis, and 17 had restrictive cardiomyopathy. We measured the pulmonary venous peak systolic and diastolic flow velocities and the systolic/diastolic flow ratio with transesophageal echocardiography during expiration and inspiration. The percent change in Doppler flow velocity from expiration to inspiration (%E) was calculated.Results. Pulmonary venous peak systolic flow in both inspiration and expiration was greater in constrictive pericarditis than in restrictive cardiomyopathy. The %E for peak systolic flow tended to be higher in constrictive pericarditis (19% vs. 10%, p = 0.09). In contrast, pulmonary venous peak diastolic flow during inspiration was lower in constrictive pericarditis than in restrictive cardiomyopathy. The %E for peak diastolic flow was larger in constrictive pericarditis (29% vs. 16%, p = 0.008). The pulmonary venous systolic/diastolic flow ratio was greater in constrictive pericarditis in both inspiration and expiration. The combination of pulmonary venous systolic/diastolic flow ratio ≥0.65 in inspiration and a %E for peak diastolic flow ≥40% correctly classified 86% of patients with constrictive pericarditis.Conclusions. The relatively larger pulmonary venous systolic/ diastolic flow ratio and greater respiratory variation in pulmonary venous systolic, and especially diastolic, flow velocities by transesophageal echocardiography can be useful signs in distinguishing constrictive pericarditis from restrictive cardiomyopathy

Breast Mass Characterization Using 3‐Dimensional Automated Ultrasound as an Adjunct to Digital Breast Tomosynthesis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135628/1/jum201332193.pd

Prevention and early detection of prostate cancer

This Review was sponsored and funded by the International Society of Cancer Prevention (ISCaP), the European Association of Urology (EAU), the National Cancer Institute, USA (NCI) (grant number 1R13CA171707-01), Prostate Cancer UK, Cancer Research UK (CRUK) (grant number C569/A16477), and the Association for International Cancer Research (AICR

Ernst Freund as Precursor of the Rational Study of Corporate Law

Gindis, David, Ernst Freund as Precursor of the Rational Study of Corporate Law (October 27, 2017). Journal of Institutional Economics, Forthcoming. Available at SSRN: https://ssrn.com/abstract=2905547, doi: https://dx.doi.org/10.2139/ssrn.2905547The rise of large business corporations in the late 19th century compelled many American observers to admit that the nature of the corporation had yet to be understood. Published in this context, Ernst Freund's little-known The Legal Nature of Corporations (1897) was an original attempt to come to terms with a new legal and economic reality. But it can also be described, to paraphrase Oliver Wendell Holmes, as the earliest example of the rational study of corporate law. The paper shows that Freund had the intuitions of an institutional economist, and engaged in what today would be called comparative institutional analysis. Remarkably, his argument that the corporate form secures property against insider defection and against outsiders anticipated recent work on entity shielding and capital lock-in, and can be read as an early contribution to what today would be called the theory of the firm.Peer reviewe

Chloride currents from the transverse tubular system in adult mammalian skeletal muscle fibers

Chloride fluxes are the main contributors to the resting conductance of mammalian skeletal muscle fibers. ClC-1, the most abundant chloride channel isoform in this preparation, is believed to be responsible for this conductance. However, the actual distribution of ClC-1 channels between the surface and transverse tubular system (TTS) membranes has not been assessed in intact muscle fibers. To investigate this issue, we voltageclamped enzymatically dissociated short fibers using a two-microelectrode configuration and simultaneously recorded chloride currents (ICl) and di-8-ANEPPS fluorescence signals to assess membrane potential changes in the TTS. Experiments were conducted in conditions that blocked all but the chloride conductance. Fibers were equilibrated with 40 or 70 mM intracellular chloride to enhance the magnitude of inward ICl, and the specific ClC-1 blocker 9-ACA was used to eliminate these currents whenever necessary. Voltage-dependent di-8-ANEPPS signals and ICl acquired before (control) and after the addition of 9-ACA were comparatively assessed. Early after the onset of stimulus pulses, di-8-ANEPPS signals under control conditions were smaller than those recorded in the presence of 9-ACA. We defined as attenuation the normalized time-dependent difference between these signals. Attenuation was discovered to be ICl dependent since its magnitude varied in close correlation with the amplitude and time course of ICl. While the properties of ICl, and those of the attenuation seen in optical records, could be simultaneously predicted by model simulations when the chloride permeability (PCl) at the surface and TTS membranes were approximately equal, the model failed to explain the optical data if PCl was precluded from the TTS membranes. Since the ratio between the areas of TTS membranes and the sarcolemma is large in mammalian muscle fibers, our results demonstrate that a significant fraction of the experimentally recorded ICl arises from TTS contributions

Genome-Wide Association Study of Retinopathy in Individuals without Diabetes

10.1371/journal.pone.0054232PLoS ONE82